Genetics and cirrhosis risk

Cirrhosis is an irreversible stage of liver disease, and patients who develop comorbidities are often at an increased risk of mortality. Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid that can develop during cirrhosis; however, some patients appear to be more susceptible than others.

In the INCA trial, Markus Casper and colleagues assessed the prevalence of NOD2 gene risk variants in patients with cirrhosis, which are thought to be associated with increased infections. In this multicenter, 2250-patient Phase II trial the frequency of NOD2 variants was 24.2%, twice as high when compared to the general population. These results suggest that the presence of NOD2 gene variants may predispose to a broad spectrum of infections in cirrhosis (abstract PS-013).

New hope for Hepatitis D patients?

Heiner Wedemeyer presented results of the phase 2 LOWR HDV-4 dose-escalation study, which aim was to assess the safety of lonafarnib for a total of 48 weeks for chronic hepatitis D treatment (abstract PS-039).

Hepatitis D always occurs in in the presence of hepatitis B virus (HBV), and leads to the most severe form of hepatitis. In 2015, the global prevalence of HBV infection in the general population was 3.5%, however, there are no current FDA-approved treatments for hepatitis d virus (HDV), which makes it difficult to treat.

In this study, 15 HDV patients were treated with a combination of lonafarnib (LNF) and ritonavir (RTV), to investigate if a rapid step-wise increase in LNF dose can allow more patients to receive higher doses. While not all patients reached full dose and two discontinued due to toxicity, LNF therapy leads to HDV RNA decline in all patients, some of which may achieve undetectable levels of HDV RNA. Individualized LNF dose escalation could become a possible strategy to overcome gastrointestinal adverse effects, allowing longer duration of regimen.

Alcohol consumption and liver disease

The majority of liver diseases are represented by alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Alcoholic hepatitis is a significant issue for millions of people, where prolonged alcohol abuse can lead to severe and irreversible liver damage. A press release presented by Fredrik Åberg (abstract GS-015) reported the results of the interaction between alcohol consumption and metabolic components in predicting severe liver disease in the general population.

Around 10-20% of heavy drinkers eventually develop cirrhosis. In this Finnish cohort, the researchers aimed to investigate which metabolic factors In 6732 patients without known liver disease, enrolled in 2000-1 and followed up until 2013. In risk drinkers, the researchers found that average alcohol consumption is associated with liver events after adjusting for age. In subjects with low to none alcohol consumption, total cholesterol, insulin resistance, age and waist circumference were the most likely predictors of severe liver disease.

As Europe has the highest average alcohol consumption worldwide, these results are of significant importance in the region. The extent of the issue is however not localized – alcohol consumption is responsible for around 6% of all deaths globally and 139 million disability adjusted life years lost due to premature deaths from alcohol.

First WHO global hepatitis report

257 million people are still infected with HBV, 68% of which in Africa and the Western Pacific

At ILC2017, the World Health Organization presented their first-ever global hepatitis report, which describes for the first time the global and regional estimates on viral hepatitis in 2015, setting the baseline for tracking progress in implementing the new strategy.

Among numerous impressive statistics, this document reports that incidence of chronic HBV infection in children under 5 reduced was from 4.7% to 1.3% thanks to immunization. However, 257 million people are still infected with HBV, 68% of which in Africa and the Western Pacific.

Viral hepatitis was responsible for 1.34 million deaths in 2015, a number comparable to deaths caused by tuberculosis, and higher than for HIV. Regarding Hepatitis C, in 2015 alone 1.75 million people worldwide became infected with the virus. Overall, the number of deaths due to hepatitis is increasing.

Testing and treatment is not always possible, but scaling up of interventions can lead to a rapid reduction in infection rates, and lower costs for diagnosis and management. Citing Mongolia as a success example, the report concludes that hepatitis elimination requires a comprehensive public health approach and innovation to achieve eradication of the disease.

Alessandro graduated in BSc Biochemistry from UCL, completing a research project on the investigation of archaeal antitermination complexes. He joined BioMed Central in 2013, and is Associate Editor for BMC Medicine.